Pancreas Disease (PD), is a viral disease affecting salmon (Atlantic salmon: Salmo salar) and rainbow trout (Oncorhynchus mykiss). It is also known as Salmon Pancreas Disease (SPD). Pancreas disease has caused extensive production losses within the Irish, Scottish and Norwegian salmonid aquaculture industries. The causative agent of PD in salmon and rainbow trout is Salmon Pancreas Disease Virus (SPDV), commonly known as salmonid alphavirus (SAV). Based on sequence data of the SAV E2 structural protein and the non-structural protein 3 (nsP3), SAV strains can be assigned to six different subtypes: SAV-1, SAV-2, SAV-3, SAV-4, SAV-5 and SAV-6). The subtype SAV-2 includes isolates which, until recently, were primarily responsible for sleeping disease (SD) outbreaks in freshwater rainbow trout (Oncorhynchus mykiss) in Europe. While all outbreaks of SD examined to date have been as a result of infection with SAV2, outbreaks of PD have been attributed to SAV-1, -2, -3, -4, -5 and -6. Interestingly, Norwegian SPD outbreaks have been mainly caused by SAV-3, with the remaining subtypes occurring in the British Isles. However, SAV-2 outbreaks have also recently been detected in Norwegian salmon populations. Horizontal transmission of SPD has been demonstrated and is believed to be the predominant transmission route, supported by the extended survival of virus in seawater. The virus is likely endemic in historically infected areas, based on evidence that outbreaks have been shown to recur in successive generations of salmon introduced on sites despite extensive fallow periods. In support of speculations that a substantial infection reservoir might exist in the seawater environment, a recent study has presented evidence of the detection of SPDV RNA in wild marine fish both in areas of salmon farming and at locations remote from aquaculture activity. Clinical signs associated with SPD include abnormal swimming behavior and lack of appetite, while characteristic histopathological signs include severe degeneration of exocrine pancreas, cardiomyopathy and skeletal myopathy. In Ireland, outbreaks have been shown to occur at all stages of the marine production cycle and involve mortality rates of up to 48%. In Norway alone, losses due to SPD have been estimated at GBP 100 million (USD 162 million) per year with an increase in production costs of NOK 6.0 (USD 1.0) per kg or NOK 14.4 million (USD 2.5 million) per 500,000 fish. Similarly in Scotland, SPD was recently estimated to account for a 10% loss of total production. Given its increasing significance and the apparent ubiquity of the causative agent, there is a clear need for enhanced controls against SPD. To date, focus has been placed on improving husbandry conditions and reducing stress in an effort to minimize losses. This approach has been complemented by the use of a commercial inactivated whole virus vaccine of the SAV-1 subtype in Ireland and Norway. However despite the commercial availability and use of this vaccine, SPD has continued to be a major problem for the Norwegian fishing industry.
Xu et al., have recently disclosed the testing of vaccines based on SAV-3: a vaccine comprising the E2 protein, a vaccine comprising the E1 protein, a DNA vaccine encoding the E2 protein, a DNA vaccine encoding the E1 protein and an inactivated whole virus vaccine. The DNA vaccines were found to be completely ineffective. In fact the onset of mortality for the groups given a primary and then boost vaccination with the DNA vaccines was 2 days earlier than the control group. Moreover this vaccination schedule with the DNA vaccines did not induce protection different from the non-vaccinated controls. The groups given a primary vaccination with the E1 DNA or E2 DNA, followed by boost with the respective protein antigen, did not show a result significantly different from controls. It was found that the inactivated vaccine induced the best protection in comparison to the sub-unit and DNA vaccines tested (Xu, et al. Superior protection conferred by inactivated whole virus vaccine over subunit and DNA vaccines against salmonid alphavirus infection in Atlantic salmon (Salmo salar L.) Vaccine 30, pp. 3918-3928 (2012)).
However it has surprisingly been found that a DNA vaccine according to the invention is not only effective, but gives far superior results compared to an inactivated whole virus PD vaccine. Thus, the disclosure herein provides the first effective nucleic acid vaccine against PD.